Project Summary: This proposal describes the organization of a comprehesive, multidisciplinary, international HIV Vaccine Trials Network (HVTN). Components of the HVTN include a Leadership Coordinating and Operations Center (L. Corey, PI;J.N.Wasserheit, Director), a Statistical and Data Management Center (S.G. Self, PI),and a Network Laboratory Program (M.J.McElrath, PI).The HVTN's mission is to provide an objective and transparent platform to evaluate candidate HIV vaccines for the prevention of HIV infection in adult and adolescent populations globally. To achieve this, the HVTN will perform safety, immunogenicity, and efficacy trials of candidate HIV vaccines and adjuvants;conduct head- to-head comparisons of candidate vaccines;develop laboratory and statistical approaches to define potential correlates of protection;design trials to estimate the effects of vaccines that reduce HIV viral set point on HIV transmission;conduct trials of candidate vaccines in special populations, such as adolescents and intravenous drug users;develop a community education program to enhance the enrollment and retention of populations at high risk for HIV acquisition;develop standardized risk reduction counseling methods;and collaborate with other NIH networks, federal agencies and non-governmental research organizations to advance the highest quality HIV vaccine research, with optimal efficiency and cost effectiveness. Relevance: The progression of the HIV epidemic, as well as the international, political, and economic toll, make a compelling case for an effective preventive HIV vaccine. While other prevention strategies offer important advances in slowing the rate of spread of HIV, the high incidence of asymptomatic persistently infected HIV-infected persons requires the development of an effective vaccine. In order to reduce the spread of this global pandemic a robust integrated laboratory and clinical trials network is a necessary driver of the HIV vaccine field.